Regulation of immunity and disease resistance by commensal microbes and chromatin modifications during zebrafish development

Jorge Galindo-Villegas, Diana Garciá-Moreno, Sofia De Oliveira, José Meseguer, Victoriano Mulero

Research output: Contribution to journalArticlepeer-review

89 Scopus citations

Abstract

How fish larvae are protected frominfection before the maturation of adaptive immunity, a process which may take up to several weeks in most species, has long been a matter of speculation. Using a germ-free model, we show that colonization by commensals in newly hatched zebrafish primes neutrophils and induces several genes encoding proinflammatory and antiviral mediators, increasing the resistance of larvae to viral infection. Commensal microbe recognition was found to be mediated mainly through a TLR/MyD88 signaling pathway, and professional phagocytes were identified as the source of these immunemediators. However, the induction of proinflammatory and antiviral genes, but not of antimicrobial effector genes, also required the covalent modification of histone H3 at gene promoters. Interestingly, chromatin modifications were not altered by commensal microbes or hatching. Taken together, our results demonstrate that gene-specific chromatin modifications are associated with the protection of zebrafish larvae against infectious agents before adaptive immunity has developed and prevent pathologies associated with excessive inflammation during development.

Original languageEnglish (US)
Pages (from-to)E2605-E2614
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number39
DOIs
StatePublished - Sep 25 2012

Keywords

  • Cytokines
  • Epigenetic
  • Evolution
  • Gene regulation
  • Live imaging

ASJC Scopus subject areas

  • General

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